It has been recognized for some time by us and other workers in the area of MALDI-MS that various components in a mixture do not enjoy the same ionization efficiency. This phenomenon frequently results in suppression of one or more components. Our objective is to characterize this phenomenon with model compounds in an effort to deal with it successfully if it cannot be overcome. Our procedure is to document the differential response of synthetic mixtures of peptides both free and chemically blocked according to amino acid composition and size as a function of matrix. Our preliminary observations are that the suppression during MALDI is not well correlated with molecular weight of the compound, but more likely correlatable with the hydrophilic character of the analyte. Our goal is to continue these assessments with a variety of matrices, with the goal of having a library of matrices available, some members of which may offer compensatory ionization efficiencies for those analytes that are expected to be suppressed in the initial matrix; this approach is expected to be especially effective in peptide mapping because the composition of a given fragment will be known and the extent to which it might be suppressed in particular matrices anticipated.